dbSNP rs11570892: LPL:c.*796A>G (chr8-19966106-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000237.3(LPL):c.*796A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,740 control chromosomes in the GnomAD database, including 2,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2476 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

LPL
NM_000237.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.150

Publications

24 publications found

Variant links:

Genes affected

LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]

LPL Gene-Disease associations (from GenCC):

familial lipoprotein lipase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
hyperlipidemia, familial combined, LPL related
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

LPL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 8-19966106-A-G is Benign according to our data. Variant chr8-19966106-A-G is described in ClinVar as Benign. ClinVar VariationId is 362428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000237.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.*796A>G		3_prime_UTR	Exon 10 of 10	NP_000228.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LPL	ENST00000650287.1	MANE Select	c.*796A>G	3_prime_UTR	Exon 10 of 10	ENSP00000497642.1
LPL	ENST00000965928.1		c.*796A>G	3_prime_UTR	Exon 12 of 12	ENSP00000635987.1
LPL	ENST00000965929.1		c.*796A>G	3_prime_UTR	Exon 10 of 10	ENSP00000635988.1

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26782

AN:

151626

Hom.:

2466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.0958

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.164

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.177

AC:

26820

AN:

151740

Hom.:

2476

Cov.:

AF XY:

0.176

AC XY:

13069

AN XY:

74090

show subpopulations

African (AFR)

AF:

0.221

AC:

9127

AN:

41384

American (AMR)

AF:

0.168

AC:

2554

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3472

East Asian (EAS)

AF:

0.0959

AC:

496

AN:

5174

South Asian (SAS)

AF:

0.154

AC:

741

AN:

4800

European-Finnish (FIN)

AF:

0.157

AC:

1638

AN:

10448

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10854

AN:

67916

Other (OTH)

AF:

0.166

AC:

348

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1095

2190

3285

4380

5475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.162

Hom.:

8142

Bravo

AF:

0.179

Asia WGS

AF:

0.150

AC:

519

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hyperlipoproteinemia, type I (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.9

(source)

DANN

Benign

0.74

PhyloP100

-0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over